TABLE 2.
HIV-1JR-FL Env variant | Cell-cell fusiona | Inhibition of cell-cell fusion (IC50) (μM)b |
Relative infectivitya | Inhibition of virus infection (IC50)c |
|||||||
---|---|---|---|---|---|---|---|---|---|---|---|
BMS-806 | BNM-III-170 | BMS-806 (nM) | BNM-III-170 (μM) | sCD4 (μg/ml) | 19b (μg/ml) | 17b (μg/ml) | 902090 (μg/ml) | VRC01 (μg/ml) | |||
Wild type | 1.00 | 0.80 | 160 | 1.00 | 7.8 | 15 | 7.3 | >30 | >30 | >30 | 0.23 |
D107R | 0.29 | 0.48 | 28 | 0.012 | 11 | 0.72 | 0.44 | 0.151 | 1.5 | 15 | 0.22 |
R166G | 0.43 | 1.1 | 208 | 0.38 | 14 | 6.5 | 2.6 | 26 | >30 | >30 | 0.21 |
D167G | 0.32 | 0.43 | 160 | 0.27 | 14 | 8.3 | 3.6 | 18 | >30 | >30 | 0.20 |
D167Q | 0.67 | 0.23 | 183 | 0.22 | 4.4 | 8.7 | 2.4 | >30 | >30 | >30 | 0.21 |
D167R | 0.92 | 0.28 | 150 | 0.17 | 6.0 | 4.8 | 3.8 | >30 | >30 | >30 | 0.21 |
E168G | 0.96 | 0.26 | 186 | 0.20 | 9.8 | 9.7 | 3.4 | >30 | >30 | >30 | 0.19 |
Y177R | 0.90 | >30 | 168 | 0.32 | 82 | 1.4 | 0.51 | 0.22 | 2.3 | >30 | 0.48 |
Y177R + D180E | 0.30 | >30 | 152 | 0.14 | >100 | 0.87 | 0.46 | 0.16 | 0.18 | >30 | 4.4 |
P183Y | 0.45 | 1.2 | 23 | 0.025 | 38 | 1.2 | 0.41 | 2.9 | >30 | >30 | 0.36 |
I184K | 0.22 | 0.19 | 26 | 0.0060 | 9.4 | 1.2 | 0.87 | 10.8 | >30 | 16 | 0.25 |
Cell-cell fusion and relative infectivity were measured as described in Materials and Methods, with the values normalized to those of the wild-type HIV-1JR-FL Env. The values represent the means of those obtained in at least three independent experiments. Values that differ more than 5-fold from the value of the wild-type HIV-1JR-FL Env are shown in boldface.
Cell-cell fusion mediated by the indicated HIV-1JR-FL variant was tested for inhibition by BMS-806, a blocker of conformational change (17, 56), and a CD4mc, BNM-III-170. The values represent the means of those obtained in at least two independent experiments. Values in boldface differ from the value of the wild-type HIV-1JR-FL by more than 5-fold.
Recombinant HIV-1 pseudotyped with the indicated HIV-1JR-FL Env was tested for inhibition by the indicated Env ligands. The 19b antibody recognizes the gp120 V3 region, the 17b antibody recognizes a CD4-induced gp120 epitope, 902090 recognizes a gp120 V2 region epitope, and VRC01 recognizes the CD4-binding site of gp120. The values represent the means of those obtained in at least two independent experiments. Values that differ from the value of the wild-type HIV-1JR-FL Env by more than 5-fold are shown in boldface.